STXTHESIS OF IODINE COMPOUNDS OF THE SALVARSAN GROUP. 1645

-~ As0 As: As: /\ /\ /A [I()*H2 /\

I!,)NHA~ IQO, I ( j X ' 0 , OH OH o, o1r OH -<2

E x P 2 R I M E N T A L .

5-Iodo-3-nitro-4- hydroxyphenylarsinic acid (I) was obtained in yields of aboutl from 3-nitro-4-hydroxyphenylarsinic acid by a slight modification of the anercuration method (R'aiziss, Kolmer, and Gavron, J . Biol. Chprrz., 1919, 40, 541; Stieglitz, Kharasch, and Hanke, J . ilmer. Chersz. Soc., 1921,43,1192). The acid darkens at 200-280" and is solu2,le in methyl alcohol, ethylene glycol, warm glycerol, formic acid, and dilute acetic acid.

5-lodo-3-nmino-4-hydroxyphenylarsinic Acid (II).-Reduction of the foregoing nitro-acid in cold alkaline solution by an excess of freshly-precipitated titanous or ferrous oxide produces the com- paratively unstable fi-iodo-S-an~ino-4-hydroxyphenylarsinic acid. Addition of zinc or lead acetat9e to the solution, neutralised with acetic acid, precipitates, in 63--66Oj, yield, the zinc or lead salt. These salts, when dry, are colourless powders of fairly constant

3L

Publ

ishe

d on

01

Janu

ary

1926

. Dow

nloa

ded

by U

nive

rsity

of

Mis

sour

i at C

olum

bia

on 0

2/09

/201

4 09

:09:

19.

View Article Online / Journal Homepage / Table of Contents for this issue

1646 MACALLUM : SYNTHESIS OF IODINE COMPOUNDS

composition (Found : As, 16.7, 17.2; I, 28.8; Zn, 10.3, 11-2; H20, 7.3. C18H1,012N313As3Zn2,5H20 requires As, 17.3 ; I, 29.4 ; Zn, 10.0; H,O, 6.9%. Found : As, 12-3, 12.3; Pb, 38.8, 38-7. C,H,O,NIAsPb requires As, 13.6 ; Pb, 37.70/). A solution of the zinc salt in cold dilute sulphuric acid (1 : 20),

when partly neutralised, furnishes the amino-acid in yellow needles which darken at about 95". The substance is apparently stable at Z O O , but decomposes with gradual loss in weight when heated in a vacuum at 65" (Found : As, 20.3 ; I, 34.2. C,H,O,NIAs requires AS, 20.9 ; I, 35.2%). 5-Iodo-3-acetylamino-4-hydroxyphenylarsinic Acid (111) .-A solu-

tion of 3.9 g. of the nitro-acid (I) in 40-80 C.C. of water and 2 C.C. of 10hT-alkali is treated at 0" with sufficient hyposulphite * powder (6-8 g. ) to bleach it. Acetic anhydride is now added a t intervals in several portions of 1 C.C. After 2-3 hours, most of the acetyl derivative will have separated, and the sulphite is then destroyed by the gradual addition of 50-60 C.C. of hydrogen peroxide (or until a drop of the solution no longer decolorises potassium tri- iodide), the solution being kept nearly neutral by suitable additions of sodium bicarbonate. Finally, the whole of the acetyl compound is precipitated (yield, 2-99 g.; 74%) by making the solution just acid to Congo paper. The washed and dried product forms a cake of colourless needles, m. p. 158-159", readiIy soluble in the alcohols or acetone (Found : As, 18.0; I, 31.1. C,H,O,NIAs requires As, 18.7; I, 31.6y0).

By recrystallisation from dilute acetic acid (1 : l ) , the acetyl compound was obtained in prisms, m. p. 190-191" (Found : As, 18.5%).

Under the above conditions, a diacetyl derivative was not pro- duced (compare King and Murch, J., 1925,127, 2632).

5-Iodo-3-carbethoxyamino-4-hydroxyphenylarsinic acid, prepared as above, ethyl chloroformate being substituted for acetic anhydride, is a powder, m. p. 182-183" (decomp.). It is soluble in methyl alcohol, acetone, or pyridine (Found : As, 17.2. CgH,lO,NIAs requires As, 17.4%). 5 : 5' - Di - iodo - 3 : 3' - diacetylarnino - 4 : 4' - dihydroxyarsenobenxene

(IV).-A solution of 2.7 g. of the preceding acetyl compound in 100 C.C.

of water containing 3 g. of sodium bicarbonate is warmed a t 55-60' with 15 g. of hyposulphite in an atmosphere of nitrogen for A 5 hours. The well-washed arseno-compound, after drying in a vacuum, is a lemon-yellow powder (yield 1.66 g.; 70y0), m. p. 194" after sintering at about 180" (Found: As, 21.1; I, 36-2.

* This is a more suitable reducing agent than titanous or ferrous oxide for the preparation of the acetyl compound.

Publ

ishe

d on

01

Janu

ary

1926

. Dow

nloa

ded

by U

nive

rsity

of

Mis

sour

i at C

olum

bia

on 0

2/09

/201

4 09

:09:

19.

View Article Online

OF THE SALVARSAN GROUP. 1647

CI6Hl4O4N2I2As2 requires As, 21.3; I, 36.1%). It is soluble in acetone, phenol, benzaldehyde, or ppidine, and its dilute solutions in alkali carbonates or hydroxides undergo little apparent change on exposure to the air.

Oxidation of the arseno-compound, suspended in aqueous bi- carbonate, with A'/lO-iodine (Required : 118 C.C. per g. Calc. for oxidation of the arseno-group : 114.6 c.c.) reproduces the original acetyla,mino-acid, m. p. 160".

5 : 5'-Di-iodo-3 : 3'-dir,itro-4 : 4'-clikydroxyarsenobenxene (VI) is a stable orange-yellow powder, darkening at about 200", obtained in 78-70% yield by treating a methyl-illcoholic solution of 5-iodo- 3-nitro-4-hydroxyphenylarsinic acid with hypophosphorous acid a t 55-60", It dissolves readily in phenol, benzaldehyde or pyridine, and, like the acetylamino-compound, is rendered water-soluble by addition of either alkali carbonate or hydroxide (Found : As, 21.9; I, 36.7.

5-lodo-3-acetylamino-4-hydroxyphenylarse~~ous oxide (V) is readily obtained by hydrolysing with aqueous bicarbonate the arsine di-iodide produced by treating with iodine a suspension of 5 : 5'-di- iodo-3 : 3'-diacetylamino-4 : 4'-dihydroxyarsenobenzene in ether. The ethereal solution of the oxide thus obta.ined is dried with sodium sulphate, the solvent evaporated at room temperature, and the residue triturated with bicarbonate solution. The oxide is a colour- less powder, rn. p. 182-183", soluble in alcohol or acetone (Found : As, 19-1 ; H,O, 6-7. C,H,0,NIAs,lQH20 requires As, 19.4; H20, 6*80,/0). 5-dodo-3-~zitro-4-hydroxyphen~Zarse?zius oxide (VII), prepared

from 5 : 5'-di-iodo-3 : 3'-dinitro-4 : 4'-dihydroxyarsenobenzene in a similar manner, is an orange-yellow powder sintering and melting indefinitely between 170" and 210". It is sparingly soluble in water, but more readily soluble in alcohol, acetone, ether, benz- aldehyde, or pyridine (Found : As, 21.2. C6H,04NIAs requires AS, 21-1y0).

Numerous attempts to prepare 5 : 5'-di-iodo-3 : 3'-diamino-4 : 4'- dihydroxyarsenobenzene from the corresponding nitro- and amino- hydroxyiodophenylarsinic acids failed to give a uniform product. It is doubtful whether the pure compound has yet been obtained.

CI2H6O,N,I,AS2 requires As, 22-1 ; I, 37-4y0).

THE LABORATORY OF THE SYNTHBTIC DRUG Co., LTD., TORONTO, CANADA. [Received, January I l th , 1926.1

Publ

ishe

d on

01

Janu

ary

1926

. Dow

nloa

ded

by U

nive

rsity

of

Mis

sour

i at C

olum

bia

on 0

2/09

/201

4 09

:09:

19.

View Article Online